The active form of vitamin D3 regulates the in vivo calcium and phosphoric acid metabolisms as well as bone metabolism through a vitamin D receptor (VDR). Vitamin D deficiency causes rachitis and osteomalacia, and the active form of vitamin D3 and its derivatives are used as therapeutic agents for these diseases. Vitamin D derivatives are used as therapeutic agents for osteoporosis in the form of oral medicines, and as therapeutic agents for psoriasis vulgaris in the form of topical agents.
The vitamin D derivatives are reported to have effects of inhibiting the growth and inducing the differentiation of malignancies (myeloid leukemia, breast cancer, prostate cancer, colon cancer, etc.), an immunomodulatory effect (therapeutic efficacy on autoimmune disease models), and a natural immunity-enhancing effect (antituberculous activity) (Non-Patent Document 1).
However, when a vitamin D derivative is administered to an animal, the effect (adverse drug reaction) of elevating blood calcium levels was difficult to be separated from other VDR-mediated actions.
Lithocholic acid, which is a bile acid, has also been verified to function as a VDR ligand (Non-Patent Document 2). Lithocholic acid acetate, which is a lithocholic acid derivative, is reported to have more potency on VDR than lithocholic acid (Non-Patent Document 3). Lithocholic acid acetate induced the differentiation of leukemic cells.
In addition to VDR, lithocholic acid also has effects of activating farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1) (Non-Patent Documents 4 and 5). Lithocholic acid acetate activated VDR more potently than lithocholic acid, but its activity on FXR was weaker than that of chenodeoxycholic acid and comparable to that of lithocholic acid (Non-Patent Document 3).    Non-Patent Document 1: Expert Opin Ther Targets Vol. 10, 2006, pp. 735-748    Non-Patent Document 2: Science Vol. 296, 2002, pp. 1313-1316    Non-Patent Document 3: J Lipid Res Vol. 46, 2005, pp. 46-57    Non-Patent Document 4: Science Vol. 284, 1999, pp 1362-1365    Non-Patent Document 5: Biochem Biophys Res Commun Vol. 298, 2002, pp 714-719